Renal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database. The renal expression levels of FX and the FXa receptors protease-activated receptor (PAR)-1 and PAR-2 were significantly higher in UUO mice than in sham-operated mice. UUO-induced tubulointerstitial fibrosis and extracellular matrix expression were suppressed in UUO mice treated with the FXa inhibitor edoxaban. Additionally, edoxaban attenuated UUO-induced macrophage infiltration and inflammatory molecule upregulation. In an analysis of the FAERS database, there were significantly fewer reports of tubulointerstitial nephritis for patients treated with FXa inhibitors than for patients not treated with inhibitors. These results suggest that FXa inhibitors exert protective effects against CKD by inhibiting tubulointerstitial fibrosis.

中文翻译：

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Xa因子抑制剂的肾脏保护作用：基础研究与数据库分析的融合。

肾小管间质损伤是一种与炎症相关的疾病，是慢性肾脏疾病（CKD）的主要原因。在各种炎症性疾病中，血凝因子活化因子X（FXa）的水平都会增加。因此，我们使用单侧输尿管梗阻（UUO）小鼠（肾小管间质纤维化模型）和美国食品药品管理局不良事件报告系统（FAERS）数据库研究了FXa抑制剂对肾小管间质损伤的保护作用。在UUO小鼠中，FX和FXa受体蛋白酶激活受体（PAR）-1和PAR-2的肾脏表达水平明显高于假手术小鼠。在用FXa抑制剂edoxaban治疗的UUO小鼠中，UUO诱导的肾小管间质纤维化和细胞外基质表达受到抑制。此外，edoxaban减弱了UUO诱导的巨噬细胞浸润和炎症分子上调。在FAERS数据库的分析中，使用FXa抑制剂治疗的患者发生肾小管间质性肾炎的报告明显少于未使用抑制剂治疗的患者。这些结果表明，FXa抑制剂通过抑制肾小管间质纤维化而发挥针对CKD的保护作用。